Dolasetron, the generic name of the compound 1H-indole-3-carboxylic acid 10-oxo-8-aza-tricyclo[5.3.1.03,8]undec-5-yl ester, is a pharmaceutically active compound widely known for its anti-emetic and anti-nausea properties. Its molecular formula responds to the following structure:

Dolasetron was described for the first time in patent EP 0266730. Said patent describes the preparation of Dolasetron and analogues compounds by a process which includes, as its last step, the esterification of 5-hydroxy-8-azatricyclo[5.3.1.03,8]-undecan-10-one (compound II) and the indole-3-carboxylic acid (compound III):

European patent application EP0339669 also describes the preparation of Dolasetron using, as the last step, the esterification reaction between compound II and the anhydride formed from the compound III and the trifluoroacetic acid.
In EP0266730 it is described the preparation of the alcohol II (scheme 1) starting from an alkyl cyclopenten-1-carboxylate, which is oxidized to a 1,2-diol using N-methyl morpholine N-oxide, and OsO4 as catalyst. This diol is then cleaved to the corresponding dialdehyde using sodium metaperiodate. A Robinson-Schöpf cyclisation of the dialdehyde with a lower alkyl glycine ester and acetonedicarboxylic acid yields the formation of a ketone. This ketone is reduced to an alcohol using sodium borohydride and the product is reacted with dihydropyran to protect the hydroxyl group. Dieckmann cyclisation using a strong base and dealkoxycarbonylation yields the desired alcohol II.

EP0339669 also describes the oxidation of the cyclopenten-1-carboxylates using ozone (Scheme 2) or m-chloroperbenzoic (Scheme 3) acid and periodic acid to obtain the corresponding dialdehyde.

Nevertheless, the processes described in said patents present some disadvantages since they show many synthetic steps, using dangerous and toxic reactants, and complex work-up. For example, the synthesis of compound II requires the use of precursors with protecting groups, thus lengthening the synthetic route and entailing a reduction of atomic efficiency. Moreover, the selected protecting group (tetrahydropyranyl) leads to a mixture of diastereoisomers instead of to a single pure product. In addition, the handling and purification of said precursor has proved to be very complex at industrial scale since said mixture has an oily consistency.
Another notable drawback is that column chromatography is used to carry out the purification of the mixture of diastereoisomers, not being possible to use other methods such as crystallization or distillation. This disadvantage, together with the reduction in the atomic efficiency remarked upon above, entails a considerable increase of residues, thus leading to environmental problems.
Furthermore, the preparation of compound II includes a process of extraction of the product from an aqueous phase with ethyl acetate which requires both, numerous steps due to the high solubility of said compound in water, and specific installations.
International application WO2007/003522 solves some of the drawbacks mentioned above, thus providing a process for the preparation of Dolasetron characterized by the fact that there is no need to use protecting groups, also showing fewer steps. The process described therein consists of an esterification reaction of an alcohol IV with indole-3-carboxylic acid; a Dieckmann reaction of the intermediate formed by reaction with a strong organic or inorganic base; and the subsequent dealcoxycarbonylation (Scheme 4).

However, there is a need in the art to provide alternative or improved methods to obtain Dolasetron by the development of new intermediates which avoid, or at least reduce, the problems described above.
On the other hand, there are documents in the state of the art which disclose some of the reactants or intermediates used in the present invention. For example, in Herrmann, J. L. et al. “Ketene thioacetal monoxides. Novel and versatile class of two-carbon Michael Receptors”, Tetrahedron Lett. 1973, 47, 4711-4714, and in Strukov, I. T. “Thiazolidinecarboxylic acid and its derivatives. I. The compound with thiazolidine-pyrrolidine ring system”, Zhurnal Obshchei Khimii. 1952, 22, 521-527, there are disclosed mono-alkylated malonates such as those used in the present invention, namely as compound of formula XIII.
In WO2006/056081 it is described the mesylate of the tricyclic ketone (R1 and R3=Ethyl) of the compound of formula IX of the present invention, this is the only salt described of a compound of such general formula.
